Recent studies describe a sex difference in fetal lung surfactant production and show that dihydrotestosterone ((DHT) can regulate this sex difference. I propose to further characterize the mechanism by which this sex difference occurs. First, the role played by the testosterone receptor in the sex defference will be studied by measuring lung surfactant (measured as phosphatidylcholine, PC, and saturated phosphatidylcholine SPC) in fetuses of the testicular feminization mouse (Tfm mouse), a model in which males are feminized because testosterone receptors are insensitive to androgen. Second, the importance of intracellular testosterone metabolism in modulating the sex difference, will be studied in two models. An inhibitor of 5a-reductase, the enzyme which converts testosterone to KHT, will be given to fetal rabbits, and PC and SPC measured to test whether the conversion of testosterone to DHT is necessary for expression of the sex difference. Also, PC and SPC will be measured in the Sebright-bantam chic embryo, a strain in which many fetal tissues, particularly the lung, aromatize androgens to estrogens. Third, I will investigate whether testosterone (or DHT) influences fetal lung surfactant production via an effect on glucocorticoid metabolism in the fetal lung. The conversion by the fetal lung of the cortisone to cortisol will be studied in fetal rabbit lung mince and the effect of testosterone or DHT on this reaction will be studied. PC and SPC will be measured in fetal Tfm mice and Sebright-bantam chick embryos in whole lung homogenate and in the rabbit fetuses in lung lavage. These will be extracted by the Folch method, the SPC fraction isolated by reaction with osmium tetroxide, and PC and SPC separated by silica gel thin layer chromatography and quantitated by phosphorous assay. The conversion of cortisone to cortisol will be measured by incubation of lung mince in media containing C-cortisone. Following extraction of the tissue and the media, measured by scintillation counting and quantitated as a percentage of original labelled cortisone. This work should yeild important imformation on the interrelationship of fetal androgen with the sex difference in fetal lung surfactant production, and should lead to greater understanding of the hormonal regulation of fetal surfactant production.